Many cellular processes involve proteins with multiple domains. This modular nature of proteins provides many advantages, providing increased stability and new cooperative functions. In addition, chimeric proteins that provide for new functional combinations can be designed from domain modules of different proteins.
The amino acid linkers that join domains can play an important role in the structure and function of multi-domain proteins. There are numerous examples of proteins whose catalytic activity requires proper linker composition. In general, altering the length of linkers connecting domains has been shown to affect protein stability, folding rates and domain-domain orientation (see George and Hering a (2003) Prot. Eng. 15:871-879). The use of linkers in the rational design of functional proteins is of interest for many purposes.
Immune responses to resolve different pathologies, such as those seen in viral infections, bacterial infections, cancer, and allergic reactions are important to the overall health of the host. Successful resolution of infections, cancer, or allergic reactions may depend on the type and magnitude of the immune response. Immunizations, whereby antigen is used to elicit further immune responses, may be helpful in successfully resolving the infections, cancers, and/or allergic reactions. It would be desirable to have a method of immunization that would enable the immune system to address all the aforementioned infections and diseases.
While vaccination protocols have been some of the great medical achievements in the last century, there are still conditions where an effective immune response has been difficult to generate. For example, human tumor immunotherapy has met with only limited success. Among the reasons for this has been the limited availability of tumor-associated antigens, and an inability to deliver such antigens in a manner that renders them immunogenic. In other instances, the need for a fast immune response is not met by current vaccine technology.
In the continual pursuit for safer and more effective vaccines, new technologies, including recombinant, purification and synthetic methods, have been used to improve the quality and specificity of antigens used. Purified, sub-unit and synthesized antigens demonstrate increased safety but diminished immunogenicity, which has been one driver for identification of effective adjuvants. Adjuvants are generally compounds, that when administered with an antigen (either in conjunction with, or given prior to the administration of the antigen) enhances and/or modifies the immune response to that particular antigen.
The present invention provides novel immunogenic compositions that exhibit improved immunogenicity; and methods of use of such compositions.
Relevant Literature
U.S. Pat. No. 6,337,191 B1; Swartz et al. U.S. Patent Published Application 20040209321; Swartz et al. International Published Application WO 2004/016778; Swartz et al. U.S. Patent Published Application 2005-0054032-A1; Swartz et al. U.S. Patent Published Application 2005-0054044-A1; Swartz et al. International Published Application WO 2005/052117. Calhoun and Swartz (2005) Biotechnol Bioeng 90(5):606-13; Jewett and Swartz (2004) Biotechnol Bioeng 86(1):19-26; Jewett et al. (2002) Prokaryotic Systems for In Vitro Expression. In: Weiner M, Lu Q, editors. Gene cloning and expression technologies. Westborough, Mass.: Eaton Publishing. p 391-411; Lin et al. (2005) Biotechnol Bioeng 89(2):148-56; Liu et al., 2005 Biotechnol Prog 21:460-465; Jewett M C and Swartz J R, 2004 Biotechnol Prog 20:102-109; Zawada and Swartz Biotechnol Bioeng, 2006. 94(4): p. 618-24.
The Im9 protein sequence is deposited at Genbank, accession number CAA33863. The structure of the protein is disclosed by Ferguson et al. (1999) J. Mol. Biol. 286:1597-1608.
Rohm et al. (1996) Virology, 217, 508-516 discusses characterization of an influenza hemaglutinin.